The specific aims of the proposal are to: (1) develop a stereospecific approach to several new cytotoxic neolignans which have been isolated in only minute quantities from A. megaphylla roots and have been shown to demonstrate inhibitor activity against cells derived from carcinoma of the nasopharynx; (2) to develop a substitution profile of the various synthetic intermediates and stereoisomers in order to correlate the structure reactivity relationships with the intent of enhancing the inhibitory activity of these neolignans against cells derived from human carcinoma of the nasopharynx; and (3) to develop a synthetic method involving a remote stereospecific epoxidation of an isolated double bond by a directive effect as one of the stereochemical controlled approaches to the family of neolignans. The methodology used in the proposal will involve synthetic organic chemistry relating to the development of a stereospecific approach to the new neolignans. The synthetic chemistry will also involve the development of a remote epoxidation method by a directive effect which should find wide application in organic synthesis. The long term objective of the proposal would be to develop a class of compounds by chemical modification that would possess specific and potent inhibitor activity against cells derived from carcinoma of the nasopharynx.